title: Nuclear magnetic resonance provides a quantitative description of protein conformational flexibility on physiologically important time scales.
abstract: A complete description of biomolecular activity requires an understanding of the nature and the role of protein conformational dynamics. In recent years, novel nuclear magnetic resonance-based techniques that provide hitherto inaccessible detail concerning biomolecular motions occurring on physiologically important time scales have emerged. Residual dipolar couplings (RDCs) provide precise information about time- and ensemble-averaged structural and dynamic processes with correlation times up to the millisecond and thereby encode key information for understanding biological activity. In this review, we present the application of two very different approaches to the quantitative description of protein motion using RDCs. The first is purely analytical, describing backbone dynamics in terms of diffusive motions of each peptide plane, using extensive statistical analysis to validate the proposed dynamic modes. The second is based on restraint-free accelerated molecular dynamics simulation, providing statistically sampled free energy-weighted ensembles that describe conformational fluctuations occurring on time scales from pico- to milliseconds, at atomic resolution. Remarkably, the results from these two approaches converge closely in terms of distribution and absolute amplitude of motions, suggesting that this kind of combination of analytical and numerical models is now capable of providing a unified description of protein conformational dynamics in solution.
authors.affiliation: Protein Dynamics and Flexibility, Institut de Biologie Structurale Jean-Pierre Ebel, CEA, CNRS, UJF UMR 5075, 41 Rue Jules Horowitz, Grenoble 38027, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Salmon
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bouvignies
authors.forename: Phineus
authors.initials: P
authors.lastname: Markwick
authors.forename: Martin
authors.initials: M
authors.lastname: Blackledge
mesh_terms: D007700:Kinetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D013997:Time Factors
chemical_list: D011506:Proteins